115 articles - From Friday Sep 02 2022 to Friday Sep 09 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Lancet Haematol |
Development of an international standard set of outcome measures for patients with venous thromboembolism: an International Consortium for Health Outcomes Measurement consensus recommendation. Additional measures can be introduced to the user by a cascade opt-in system that allows for further assessment if required. This set of outcomes and measurement tools will facilitate the implementation of the use of patient-centred outcomes in daily practice. |
meta-analyses and systematic reviews
| Blood Adv |
Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: A systematic review and meta-analysis. Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time-to-response, and improves exacerbation rates, at the expense of increased relapse and bleeding risk. |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Cancer risk and gammopathies in 2123 adults with Gaucher disease type 1 in the International Gaucher Group Gaucher Registry. Colorectal, prostate, and lung cancer risks were lower than expected. These findings help advance care of patients with GD1 by supporting recommendations for individualized monitoring for malignancies and antecedents such as MGUS for MM and provoke important questions of the role of glucosylceramide and related sphingolipids in cancer biology. |
Contemporary outcomes in IDH-mutated AML: The impact of co-occurring NPM1 mutations and venetoclax-based treatment. Differing outcomes were observed in IDH1 mut vs IDH2 mut or NPM1 mut AML which were influenced by co-occurring NPM1 mutations and partially abrogated with venetoclax-based therapy. Given the differing biology and survival in IDH1 mut AML, investigations incorporating molecularly targeted therapies such as IDH inhibitors remain warranted in this subgroup. |
Converting Adults with Sickle Cell Disease from Full Agonist Opioids to Buprenorphine: A Reliable Method with Safety and Early Evidence of Reduced Acute Care Utilization. At six months follow-up, five participants had discontinued buprenorphine (16.67%), and overall acute care visits dropped from a mean of 10.50 (SD 11.35) in the six months pre-induction to 2.89 (SD 3.40) in the six months post induction. In an appropriately interdisciplinary care setting, buprenorphine shows promise as a safe alternative to chronic opioid therapy with early evidence of benefit for high utilizing patients with SCD. |
Efficacy of pp65-specific TCR-T cell therapy in treating cytomegalovirus infection after hematopoietic stem cell transplantation. Among them, 2 patients have survived for more than one year. This study demonstrates the great potential in the treatment and prevention of CMV infection following HSCT or other organ transplantation. |
Erythroferrone contributes to iron mobilization for embryo erythropoiesis in iron-deficient mouse pregnancies. The effect was exacerbated under iron-deficient conditions where ERFE KO embryos had higher hepcidin, lower Hb and Hct, and lower brain iron concentration compared to WT embryos, indicative of iron restriction. Thus, under iron-deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis. |
Functional role of endothelial transferrin receptor 1 in iron sensing and homeostasis. Finally, ferritin and non-transferrin bound iron (NTBI) are additional sources of iron that mediate Bmp6 induction in primary liver endothelial cell cultures via TFR1-independent mechanisms. Together, our data demonstrate a minor functional role for endothelial cell TFR1 in iron uptake, BMP6 regulation, and hepatocyte hepcidin regulation under iron limiting conditions, and suggest that ferritin and/or NTBI uptake by other transporters have a dominant role when iron availability is high. |
Long-term outcomes and predictors of early response, late relapse and survival for patients treated with bispecific LV20.19 CAR T-cells. Bridging therapy and higher absolute lymphocyte count on day of CAR-T infusion were associated with inferior survival outcomes. In conclusion, this initial trial of LV20.19 CAR-T demonstrates a signal for favorable long-term outcomes for patients with R/R B-cell malignancies. |
Low-dose dasatinib 50 The rate of any grade pleural effusion was 5% with dasatinib 50 |
Ponatinib after failure of second-generation tyrosine kinase inhibitor in resistant chronic-phase chronic myeloid leukemia. Ponatinib shows high response rates and robust survival outcomes in patients whose disease failed prior to 2G TKIs, including patients with T315I mutation. The response-based dosing in OPTIC led to improved safety and similar efficacy outcomes compared with PACE. |
Retrospective comparison of survival and responses to Fludarabine, Cytarabine, GCSF (FLAG) in combination with gemtuzumab ozogamicin (GO) or Idarubicin (IDA) in patients with newly diagnosed core binding factor (CBF) acute myelogenous leukemia: MD Anderson experience in 174 patients. FLAG-GO regimen was superior in optimal disease specific fusion transcript reduction at end of induction (p=0.002,), mid-consolidation (p<0.01) and end of consolidation (p<0.001) therapy. Induction/consolidation with FLAG-GO regimen results in better clinical outcomes in newly diagnosed patients with CBF-AML compared to FLAG-IDA and achieves deeper molecular clearance by qPCR assessment of the fusion transcripts. |
Revised MALT-IPI: A new predictive model that identifies high-risk patients with extranodal marginal zone lymphoma. Revised MALT-IPI is a new index centered on disease characteristics that provides robust risk-stratification identifying a group of patients characterized by earlier progression of disease. Revised MALT-IPI can allow a more disease-adjusted management of patients with EMZL in clinical trials and practice. |
Safety and Efficacy of Jaktinib in the Treatment of Janus Kinase Inhibitor-Naïve Patients with Myelofibrosis: Results of a Phase II Trial. All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability. |
The significance of spleen size in children with sickle cell anemia. Finally, we found a strong association between erythrocyte deformability measured with oxygen gradient ektacytometry, spleen size, and PIT counts. In conclusion, our results do not agree with the general perception that most children with SCA undergo autosplenectomy within the first decade of life and indicate that loss of erythrocyte deformability contributes to loss of splenic filtration capacity in SCA, as well as phenotypical variations in spleen size. |
Time-dependent prediction of mortality and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation using machine learning. These gradient boosting machine models provide well-calibrated, time-dependent risk predictions and achieved areas under the receiver-operating characteristic of 0.92 and 0.83 and areas under the precision-recall curve of 0.58 and 0.62 for prediction of mortality and CMV reactivation, respectively, in a 21-day time window. Both models were successfully validated in a prospective, non-interventional study and performed on par with expert hematologists in a pilot comparison. |
Transferrin receptor 2 (Tfr2) genetic deletion makes transfusion-independent a murine model of transfusion-dependent ß-thalassemia. Remarkably, BM Tfr2 deletion is also sufficient to avoid long-term blood transfusions required for survival of Hbb th1/th2 animals, preventing mortality due to chronic anemia and reducing transfusion-associated complications, such as progressive iron-loading. Altogether, TFR2 targeting might represent a promising therapeutic option also for TDT. |
Understanding pulse oximetry in hematology patients: Hemoglobinopathies, racial differences and beyond. In addition, a range of challenges may arise in patients with increased levels of methemoglobin - whether acquired or inherited - carboxyhemoglobin, or in patients with a subset of inherited variant hemoglobins. It is important for Hematologists, and indeed al clinicians who rely on pulse oximetry, to understand the principles and limitations of this ubiquitous test. |
| Ann Oncol |
An international open-label randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer. This trial provides some evidence that the two-step approach is an alternative option for cancer pain management. |
| Blood |
A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and wellbeing. Iron repletion did not affect any cognition or wellbeing measures. These data provide evidence that current criteria for blood donation preserve red cell transfusion quality for the recipient and protect adult donors from measurable effects of blood donation-induced iron deficiency on cognition. |
Antigen-guided depletion of anti-HLA antibody-producing cells by HLA-Fc fusion proteins. These results support HLA-Fc as a novel strategy for antigen-specific humoral suppression to improve transfusion and transplantation outcomes. With the long-term goal of targeting HLA-specific memory B cells for desensitization, further studies of HLA-Fc's efficacy in immune-competent animal models are warranted. |
Epo-IGF1R crosstalk expands stress-specific progenitors in regenerative erythropoiesis and myeloproliferative neoplasm. In myeloproliferative neoplasm patient samples, the number of sCFU-E like cells increases, and inhibition of IGR1R/IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identify a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis. |
Perioperative diagnosis and impact of acquired von Willebrand syndrome in infants with congenital heart disease. The GPIbM/VWF:Ag ratio is a reliable test that can be included in routine intraoperative laboratory workup. Our data provide the basis for further studies in larger patient cohorts to achieve definitive clarification of the effects of aVWS and its potential treatment on intraoperative bleeding. |
| Blood Adv |
A conformational transition of the D'D3 domain primes von Willebrand factor for multimerization. Furthermore, we find a stabilization of the interface in the presence of coagulation factor VIII, providing evidence for a previously hypothesized binding site in submodule C8-3. Our findings highlight the critical role of the D'D3 domain in VWF biosynthesis and function, and we anticipate our methodology to be applicable to study other, similar conformational changes in VWF and beyond. |
Long-term proliferation of immature hypoxia-dependent JMML cells supported by a 3D in vitro system. Our study contributes to the development of a robust JMML 3D in vitro model to study and define the impact of microenvironment stimuli on JMML disease and the molecular mechanisms regulating JMML initiating and propagating cells. Pd-JAO may become a promising model for compound tests focusing on new therapeutic intervention aiming to eradicate JMML progenitors and control JMML disease. |
Proinflammatory microenvironment promotes lymphoma progression in mice with high megakaryocyte and TPO levels. Moreover, RNA sequencing of blood-resident Eµ-myclymphoma cells from TpoTgand wild-type mice after tumour transplant revealed upregulation of hallmark gene sets associated with inflammatory response in TpoTg mice. We propose that a pro-inflammatory microenvironment in TpoTgmice promoted lymphoma progression. |
Prospective hemophilia inhibitor PUP study reveals distinct antibody signatures during FVIII inhibitor eradication. Interestingly, one patient with partial ITI success and one patient with ITI failure developed apparent oligoreactive FVIII-binding antibodies during ITI. The explanation of the true nature of these antibodies requires more comprehensive follow-ups in future studies. |
Sickle cell disease is a risk factor for transplant-associated thrombotic microangiopathy in children. In available pre-HCT samples, there were no differences in complement biomarkers in those with SCD and those without, though SCD patients did have significantly higher markers of endothelial activation, sVCAM-1 and p-selectin levels. In conclusion, children with SCD merit careful screening for TA-TMA post HCT, particularly those receiving a haploidentical HCT. |
TCRvß-CART therapy mediates high precision targeting of malignant T-cell clones. Importantly, in al cases the non-targeted TCRvb families were spared. Thus, TCRvb-CART therapy provides a potential option for high-precision treatment of PTCL with limited healthy T-cell depletion. |
The outcome of older adults with classic Hodgkin lymphoma in British Columbia. With a median follow-up of 9 years, 5-year disease specific (DSS) and overall survival (OS) have improved by decade comparison (both p 70 even in the mod-ern treatment era. Further, treatment-related toxicity remains a significant concern and use of bleo-mycin should be avoided in most patients. |
Uncoupling of platelet granule release and integrin activation suggests GPIIb/IIIa as therapeutic target in COVID-19. These thrombi were susceptible to subthreshold levels of GPIIb/IIIa blockers eptifibatide or tirofiban that had only a minor effect in control blood. We provide evidence that low dose GPIIb/IIIa blockade could be a therapeutic approach in COVID-19. |
| Blood Cancer J |
Clinical outcomes in patients with chronic lymphocytic leukemia with disease progression on ibrutinib. Among patients with CLL disease progression on ibrutinib, OS was significantly longer when next-line treatment was chimeric antigen receptor T-cell therapy (median not reached) or venetoclax-based treatment (median 29.8 |
Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial. There was no statistically significant difference in EFS, OS, CR, or toxicity between ADE and DA regimens in pediatric AML. The trial was registered with the Clinical Trial Registry of India (Reference number: CTRI/2014/11/005202). |
| Haematologica |
Activation of lncRNA NEAT1 leads to survival advantage of multiple myeloma cells by supporting a positive regulatory loop with DNA repair proteins. Overall, we provided novel important insights into NEAT1 role in supporting MM cells adaptation to stressful conditions by improving the maintenance of DNA integrity. Taken together, our results suggest that NEAT1, and probably PS organelles, could represent a potential therapeutic target for MM treatment. |
Targeting dual oncogenic machineries driven by TAL1 and PI3K-AKT pathways in Tcell acute lymphoblastic leukemia. TAL1-positive, AKT-activated T-ALL cells were very sensitive to PIK-75, as evidenced by the growth inhibition and apoptosis induction, while T-ALL cells that exhibited activation of the JAK-STAT pathway were insensitive to this drug. Together, our study demonstrates a strategy targeting two types of core machineries mediated by oncogenic transcription factors and signaling pathways in T-ALL. |
| J Hematol Oncol |
Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1. We found that circPDK1 was activated by HIF1A at the transcriptional level by modulating the miR-628-3p/BPTF axis and degrading BIN1. Exosomal circPDK1 is a promising biomarker for PC diagnosis and prognosis and represents a potential therapeutic target for PC. |
Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation. In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making. |
Somatic copy number alteration and fragmentation analysis in circulating tumor DNA for cancer screening and treatment monitoring in colorectal cancer patients. In summary, we developed and validated a sensitive and cost-effective method for untargeted ctDNA detection at diagnosis as well as for treatment monitoring of al CRC patients based on genetic as well as non-genetic tumor-specific cfDNA features. Thus, once sensitivity and specificity have been externally validated, LIFE-CNA has the potential to be implemented into clinical practice. To the best of our knowledge, this is the first study to consider multiple genetic and non-genetic cfDNA features in combination with ML classifiers and to evaluate their potential in both cancer detection and treatment monitoring. |
| Lancet Haematol |
Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Interpretation Azacitidine with venetoclax is safe and shows encouraging activity in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia. Funding MD Anderson Cancer Center. |
Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Interpretation The durability of improved haematological outcomes and favourable safety profile over 48 weeks of treatment suggests that pegcetacoplan has the potential to improve treatment benefit and alter treatment goals in patients with paroxysmal nocturnal haemoglobinuria. Funding Apellis Pharmaceuticals. |
| Leukemia |
Pregnancy and childbirth outcomes in women with myeloproliferative neoplasms-a nationwide population-based study of 342 pregnancies in Sweden. Incidence was 12.2 per 100.000 pregnancies. In summary, preterm birth was an important complication in MPN pregnancies, while maternal complications were less common than previously reported. |
Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms - results of the EUROPE trial by EMSCO. Sequential analysis of variant allelic frequency of mutations like SRSF2 did not reveal an impact of ROM on clonal evolution in both responders and non-responders. In summary, our study confirms the safety and efficacy of ROM in LR-MDS patients and may allow to better define subgroups of patients with a high likelihood of response. |
Protein tyrosine kinase 2b inhibition reverts niche-associated resistance to tyrosine kinase inhibitors in AML. Our data suggest that the leupaxin-PTK2B axis plays an important role in acquired TKI resistance in AML. PTK2B/FAK inhibitors act synergistically with currently used therapeutics and may overcome emerging TKI resistance in FLT3-mutated AML at an early timepoint. |
| Thromb Haemost |
Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study. GFC/LT evidenced fibrinolysis activation during cesarean delivery, linked to a decrease in fibrinolytic inhibitors. GFC/LT revealed a significant antifibrinolytic effect of TXA compared with placebo. |
Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions. Novel parenteral antiplatelet drugs, such as cangrelor, selatogrel, and zalunfiban, have been recently developed to achieve rapid, potent antiplatelet effects while preserving hemostasis. We provide a description of currently available parenteral antiplatelet agents and of those in clinical development for prehospital administration in STEMI patients. |
Protein Tyrosine Phosphatase 1B Deficiency in Vascular Smooth Muscle Cells Promotes Perivascular Fibrosis following Arterial Injury. SMAD2 siRNA transfection increased protein levels of PDGFRß and MYH10 while reducing ERK1/2 phosphorylation, thus phenocopying genetic PTP1B deletion. Chronic reduction of PTP1B in SMCs promotes dedifferentiation, perivascular fibrosis, and adverse remodeling following vascular injury by mechanisms involving an ERK1/2 phosphorylation-driven shift from SMAD2 to KLF4-regulated gene transcription. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Am J Hematol |
The Forgotten Survivor: A comprehensive review on Non-Hodgkin Lymphoma Survivorship. The latter includes CAR T-cell therapy, monoclonal antibodies, checkpoint inhibitors, and hematopoietic stem cell transplantation. In this report, we aim to shed the light on these aspects in addition to discuss survivorship care plan for NHL. |
| Blood |
| Blood Cancer J |
Smoldering multiple myeloma current treatment algorithms. Patients with newly diagnosed high risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials. Patients with low risk SMM should be observed without therapy every 3-4 months. |
| J Hematol Oncol |
ASXL1/2 mutations and myeloid malignancies. ASXL1 mutations frequently occur in myeloid malignancies and are associated with a poor prognosis, whereas ASXL2 mutations frequently occur in AML with t(8; 21)/RUNX1-RUNX1T1 and less frequently in other subtypes of myeloid malignancies. Herein, we review the role of ASXL1 and ASXL2 in normal and malignant hematopoiesis by summarizing the findings of mouse model systems and discussing their underlying molecular mechanisms. |
| Lancet Haematol |
Achieving access to haemophilia care in low-income and lower-middle-income countries: expanded Humanitarian Aid Program of the World Federation of Hemophilia after 5 years. In response to the programme, some governments increased investment in haemophilia care, including independent purchases of small amounts of treatment products. With unparalleled scope and complexity, and substantial benefits to people with haemophilia and society in general, the WFH HAP is an exemplar of partnership between for-profit and not-for-profit organisations advancing health-care equity in LICs and LMICs, which could be replicated by other organisations supporting people with different monogenic diseases. |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| CA Cancer J Clin |
| Haematologica |
| Lancet Haematol |
Letters to the editors and authors’ replies
| Am J Hematol |
Clinical outcomes and impact of therapeutic intervention in patients with acute myeloid leukemia who experience measurable residual disease (MRD) recurrence following MRD-negative remission. Recurrence of MRD in AML is associated with imminent relapse unless intervened upon. Change in chemotherapy regimen and/or immediate transplant improve outcomes. |
The Prevalence and Clinical Outcomes of Microangiopathic Hemolytic Anemia in Patients with Biopsy Proven Renal Thrombotic Microangiopathy. The clinical spectrum of renal thrombotic microangiopathy (TMA) includes both the classic "Hemolytic uremic syndrome" (HUS) and a "Renal limited TMA" without systemic microangiopathic hemolytic anemia (MAHA). |
| Blood Cancer J |
| Lancet Haematol |